The initiation of long-lasting, tumor-specific and tumor-rejecting immunity in murine models has been produced by methods requiring syngeneic tumor cells plus adjuvant. When the principles were carefully adhered to in clinical trials, some unequivocal and very encouraging regressions have been seen, induced solely by immunotherapy. A major limitation restricting human application has become apparent: the quantity of autologous tumor cells required is very large and usually not available. Hybrid tumor cells offer a solution and several potential advantages for specific immunotherapy: they are formed by fusion of the target autologous/syngeneic tumor cells with a second cell line in culture. Their advantages are: (1) they can be grown in culture to produce unlimited quantities, (2) they express on their cell surfaces the required immunizing tumor specific antigens (empirical evidence of this), (3) they can be administered "live" as they bear foreign histocompatibility antigens and are eliminated by the ensuing immune response. We propose in this research to do the following: (1) to determine if the concept of hybrid tumor cell immunotherapy is practical and effective in selected animal cancer models, (2) to determine if there are parameters by which hybrid clones of maximal immuogenicity can be selected, (3) to determine if human hybrid tumor cell lines can consistently and expeditiously be produced in large quantities and we will evaluate selected characteristics of these lines. The cell fusion will employ polyethylene glycol (PEG) as fusogen. The animal and human cell lines selected for fusion with tumors will be deficient in the enzyme HGPRT to allow selective growth of hybrids in HAT medium. Flow cytometry will be employed in (1) confirming the production of authentic hybrids, (2) characterizing their H-2 and HLA expression by indirect immunofluorescence, and (3) sorting hybrids by density of antigen expression to determine correlates with immunogenicity.